Background General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP. Methods This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m 2 , and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H 2 O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H 2 O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H 2 O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pa o 2 /inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure. Results Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H 2 O. Pa o 2 /inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H 2 O), and 305 (fixed PEEP of 4 to 5 cm H 2 O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H 2 O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H 2 O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H 2 O) and 26.8% (fixed PEEP of 4 to 5 cm H 2 O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H 2 O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H 2 O). Mean intraoperative driving pressure was 9.8 cm H 2 O (individualized PEEP), 14.4 cm H 2 O (fixed PEEP of 12 cm H 2 O), and 18.8 cm H 2 O (fixed PEEP of 4 to 5 cm H 2 O), P < 0.001. Conclusions This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear. Editor’s Perspective What We Already Know about This Topic Optimal methods for preserving lung function in obese patients remain controversial. Previous studies in laparoscopic abdominal surgery have focused on the use of different levels of positive end-expiratory pressure (PEEP; either fixed or individualized based on measures of distribution of ventilation or lung compliance) with or without use of recruitment maneuvers. Electrical impedance tomography is a real time tool that allows visualization of distribution of ventilation and calculation of indices of regional inhomogeneity of ventilation, which may predict postoperative lung function. The authors combined the locally acquired data from two randomized controlled trials of such patients, an earlier physiologic study and a later subset of patients from a large multinational study (PROBESE) evaluating as a primary outcome oxygenation (Pa o 2 /F io 2 ratio). They compared high or low fixed PEEP levels with or without recruitment and individualized PEEP using electrical impedance tomography. What This Article Tells Us That Is New Individualized positive end-expiratory pressure (PEEP; median 18 cm H 2 0) was superior to either fixed low levels (4 to 5 cm H 2 0) or a higher level (12 cm H 2 0 with recruitment) with regards to oxygenation, driving pressures, and indices of regional ventilation. Despite improvement in lung function, no differences in postoperative pulmonary complications were observed. However, this cohort was not adequately powered for clinical outcomes.

Background Protective ventilation may improve outcomes after major surgery. However, in the context of one-lung ventilation, such a strategy is incompletely defined. The authors hypothesized that a putative one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after thoracic surgery. Methods The authors merged Society of Thoracic Surgeons Database and Multicenter Perioperative Outcomes Group intraoperative data for lung resection procedures using one-lung ventilation across five institutions from 2012 to 2016. They defined one-lung protective ventilation as the combination of both median tidal volume 5 ml/kg or lower predicted body weight and positive end-expiratory pressure 5 cm H 2 O or greater. The primary outcome was a composite of 30-day major postoperative pulmonary complications. Results A total of 3,232 cases were available for analysis. Tidal volumes decreased modestly during the study period (6.7 to 6.0 ml/kg; P < 0.001), and positive end-expiratory pressure increased from 4 to 5 cm H 2 O ( P < 0.001). Despite increasing adoption of a “protective ventilation” strategy (5.7% in 2012 vs. 17.9% in 2016), the prevalence of pulmonary complications did not change significantly (11.4 to 15.7%; P = 0.147). In a propensity score matched cohort (381 matched pairs), protective ventilation (mean tidal volume 6.4 vs. 4.4 ml/kg) was not associated with a reduction in pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32). In an unmatched cohort, the authors were unable to define a specific alternative combination of positive end-expiratory pressure and tidal volume that was associated with decreased risk of pulmonary complications. Conclusions In this multicenter retrospective observational analysis of patients undergoing one-lung ventilation during thoracic surgery, the authors did not detect an independent association between a low tidal volume lung-protective ventilation regimen and a composite of postoperative pulmonary complications. Editor’s Perspective What We Already Know about This Topic Lower tidal volume ventilation with moderate positive end-expiratory pressure (PEEP) compared with higher tidal volumes with low PEEP is associated with fewer pulmonary complications in adult respiratory distress syndrome and in abdominal surgery with two-lung ventilation. Fewer studies have assessed optimal ventilation strategies for thoracic surgery with one-lung ventilation. Optimal lung protective strategies for one-lung ventilation are undefined. What This Article Tells Us That Is New This five-center retrospective observational study evaluated records from 3,232 thoracic surgical patients who underwent one-lung ventilation for pneumonectomies, bilobectomies, single lobectomies, segmentectomies, or wedge resections. Patients with tidal volumes 5 ml/kg or lower and PEEP greater than 5 cm H 2 O did not have significantly different 30-day adverse pulmonary outcomes compared with patients not ventilated with this strategy. Higher mechanical ventilation driving pressures were not associated with composite 30-day adverse pulmonary outcome. The protective ventilation regimen tested was not associated with decreased pulmonary complications.

The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.

Background Mechanical ventilation with low tidal volumes has the potential to mitigate ventilation-induced lung injury, yet the clinical effect of tidal volume size on myocardial function has not been clarified. This cross-sectional study investigated whether low tidal volume ventilation has beneficial effects on myocardial systolic and diastolic function compared to intermediate tidal volume ventilation. Methods Forty-two mechanically ventilated patients without acute respiratory distress syndrome (ARDS) underwent transthoracic echocardiography after more than 24 h of mechanical ventilation according to the Protective Ventilation in Patients without ARDS (PReVENT) trial comparing a low versus intermediate tidal volume strategy. The primary outcome was left ventricular and right ventricular myocardial performance index as measure for combined systolic and diastolic function, with lower values indicating better myocardial function and a right ventricular myocardial performance index greater than 0.54 regarded as the abnormality threshold. Secondary outcomes included specific systolic and diastolic parameters. Results One patient was excluded due to insufficient acoustic windows, leaving 21 patients receiving low tidal volumes with a tidal volume size (mean ± SD) of 6.5 ± 1.8 ml/kg predicted body weight, while 20 patients were subjected to intermediate tidal volumes receiving a tidal volume size of 9.5 ± 1.6 ml/kg predicted body weight (mean difference, −3.0 ml/kg; 95% CI, −4.1 to −2.0; P < 0.001). Right ventricular dysfunction was reduced in the low tidal volume group compared to the intermediate tidal volume group (myocardial performance index, 0.41 ± 0.13 vs . 0.64 ± 0.15; mean difference, −0.23; 95% CI, −0.32 to −0.14; P < 0.001) as was left ventricular dysfunction (myocardial performance index, 0.50 ± 0.17 vs . 0.63 ± 0.19; mean difference, −0.13; 95% CI, −0.24 to −0.01; P = 0.030). Similarly, most systolic parameters were superior in the low tidal volume group compared to the intermediate tidal volume group, yet diastolic parameters did not differ between both groups. Conclusions In patients without ARDS, intermediate tidal volume ventilation decreased left ventricular and right ventricular systolic function compared to low tidal volume ventilation, although without an effect on diastolic function. Editor’s Perspective What We Already Know about This Topic Lower tidal volume mechanical ventilation is associated with reduced ventilation induced lung injury What This Article Tells Us That Is New What is not known is if lower versus intermediate tidal volume mechanical ventilation is also associated with improved systolic and diastolic left ventricular and right ventricular myocardial function This study of 42 mechanically ventilated patients who did not have acute respiratory distress syndrome found that lower tidal volume mechanical ventilation was associated with increased right and left ventricular systolic function but not improved diastolic function

Background In acute respiratory failure elevated intraabdominal pressure aggravates lung collapse, tidal recruitment, and ventilation inhomogeneity. Low positive end-expiratory pressure (PEEP) may promote lung collapse and intrapulmonary shunting, whereas high PEEP may increase dead space by inspiratory overdistension. The authors hypothesized that an electrical impedance tomography–guided PEEP approach minimizing tidal recruitment improves regional ventilation and perfusion matching when compared to a table-based low PEEP/no recruitment and an oxygenation-guided high PEEP/full recruitment strategy in a hybrid model of lung injury and elevated intraabdominal pressure. Methods In 15 pigs with oleic acid–induced lung injury intraabdominal pressure was increased by intraabdominal saline infusion. PEEP was set in randomized order: (1) guided by a PEEP/inspired oxygen fraction table, without recruitment maneuver; (2) minimizing tidal recruitment guided by electrical impedance tomography after a recruitment maneuver; and (3) maximizing oxygenation after a recruitment maneuver. Single photon emission computed tomography was used to analyze regional ventilation, perfusion, and aeration. Primary outcome measures were differences in PEEP levels and regional ventilation/perfusion matching. Results Resulting PEEP levels were different (mean ± SD) with (1) table PEEP: 11 ± 3 cm H 2 O; (2) minimal tidal recruitment PEEP: 22 ± 3 cm H 2 O; and (3) maximal oxygenation PEEP: 25 ± 4 cm H 2 O; P < 0.001. Table PEEP without recruitment maneuver caused highest lung collapse (28 ± 11% vs. 5 ± 5% vs. 4 ± 4%; P < 0.001), shunt perfusion (3.2 ± 0.8 l/min vs. 1.0 ± 0.8 l/min vs. 0.7 ± 0.6 l/min; P < 0.001) and dead space ventilation (2.9 ± 1.0 l/min vs. 1.5 ± 0.7 l/min vs. 1.7 ± 0.8 l/min; P < 0.001). Although resulting in different PEEP levels, minimal tidal recruitment and maximal oxygenation PEEP, both following a recruitment maneuver, had similar effects on regional ventilation/perfusion matching. Conclusions When compared to table PEEP without a recruitment maneuver, both minimal tidal recruitment PEEP and maximal oxygenation PEEP following a recruitment maneuver decreased shunting and dead space ventilation, and the effects of minimal tidal recruitment PEEP and maximal oxygenation PEEP were comparable. Editor’s Perspective What We Already Know about This Topic In acute lung injury, the optimal positive end-expiratory pressure (PEEP) strategy for mechanical ventilation is not known. What This Article Tells Us That Is New In a porcine model of induced acute lung injury, with increased abdominal pressure caused by intraperitoneal saline infusion, using a crossover design, tracheostomized animals were ventilated using: (1) positive end-expiratory pressure (PEEP) table–based low PEEP without lung recruitment; (2) minimal tidal recruitment PEEP guided by electrical impedance tomography with recruitment; and (3) maximal oxygenation PEEP with recruitment. Using a PEEP table and no recruitment, compared with recruitment and either minimal tidal recruitment PEEP or maximal oxygenation PEEP, resulted in less delivered PEEP, and more lung collapse and regional ventilation/perfusion mismatch. The latter two methods had comparable results.

Background Pneumoperitoneum and a steep Trendelenburg position during robot-assisted laparoscopic prostatectomy have been demonstrated to promote a cranial shift of the diaphragm and the formation of atelectasis in the dorsal parts of the lungs. However, neither an impact of higher positive end-expiratory pressure (PEEP) on preserving the ventilation in the dorsal region nor its physiologic effects have been fully examined. The authors hypothesized that PEEP of 15 cm H 2 O during robot-assisted laparoscopic prostatectomy might maintain ventilation in the dorsal parts and thus improve lung mechanics. Methods In this randomized controlled study, 48 patients undergoing robot-assisted laparoscopic prostatectomy were included in the analysis. Patients were assigned to the conventional PEEP (5 cm H 2 O) group or the high PEEP (15 cm H 2 O) group. Regional ventilation was monitored using electrical impedance tomography before and after the establishment of pneumoperitoneum and 20° Trendelenburg position during the surgery. The primary endpoint was the regional ventilation in the dorsal parts of the lungs while the secondary endpoints were lung mechanics and postoperative lung function. Results Compared to that in the conventional PEEP group, the fraction of regional ventilation in the most dorsal region was significantly higher in the high PEEP group during pneumoperitoneum and Trendelenburg position (mean values at 20 min after taking Trendelenburg position: conventional PEEP, 5.5 ± 3.9%; high PEEP, 9.9 ± 4.7%; difference, –4.5%; 95% CI, –7.4 to –1.6%; P = 0.004). Concurrently, lower driving pressure (conventional PEEP, 14.9 ± 2.5 cm H 2 O; high PEEP, 11.5 ± 2.8 cm H 2 O; P < 0.001), higher lung dynamic compliance, and better oxygenation were demonstrated in the high PEEP group. Postoperative lung function did not differ between the groups. Conclusions Application of a PEEP of 15 cm H 2 O resulted in more homogeneous ventilation and favorable physiologic effects during robot-assisted laparoscopic prostatectomy but did not improve postoperative lung function. Editor’s Perspective What We Already Know about This Topic Pneumoperitoneum and steep Trendelenburg during laparoscopic prostatectomy shift the diaphragm cephalad and cause atelectasis in the dorsal lungs The ability of positive end-expiratory pressure to mitigate these effects remains controversial What This Article Tells Us That Is New In patients undergoing robot-assisted laparoscopic prostatectomy, 15 but not 5 cm H 2 O of positive end-expiratory pressure increased ventilation in the dorsal parts of the lung, resulting in more normal lung mechanics and gas exchange High positive end-expiratory pressure did not improve postoperative lung function

Editor’s Perspective What We Already Know about This Topic Recommendations for anesthetic care are often difficult to implement in the intraoperative setting because of the requirement for continuous attention What This Article Tells Us That Is New Closed-loop, automated management of anesthetic, analgesic, fluid, and ventilation parameters was superior to manual control and might influence postoperative outcomes Background Cognitive changes after anesthesia and surgery represent a significant public health concern. We tested the hypothesis that, in patients 60 yr or older scheduled for noncardiac surgery, automated management of anesthetic depth, cardiac blood flow, and protective lung ventilation using three independent controllers would outperform manual control of these variables. Additionally, as a result of the improved management, patients in the automated group would experience less postoperative neurocognitive impairment compared to patients having standard, manually adjusted anesthesia. Methods In this single-center, patient-and-evaluator-blinded, two-arm, parallel, randomized controlled, superiority study, 90 patients having noncardiac surgery under general anesthesia were randomly assigned to one of two groups. In the control group, anesthesia management was performed manually while in the closed-loop group, the titration of anesthesia, analgesia, fluids, and ventilation was performed by three independent controllers. The primary outcome was a change in a cognition score (the 30-item Montreal Cognitive Assessment) from preoperative values to those measures 1 week postsurgery. Secondary outcomes included a battery of neurocognitive tests completed at both 1 week and 3 months postsurgery as well as 30-day postsurgical outcomes. Results Forty-three controls and 44 closed-loop patients were assessed for the primary outcome. There was a difference in the cognition score compared to baseline in the control group versus the closed-loop group 1 week postsurgery (–1 [–2 to 0] vs. 0 [–1 to 1]; difference 1 [95% CI, 0 to 3], P = 0.033). Patients in the closed-loop group spent less time during surgery with a Bispectral Index less than 40, had less end-tidal hypocapnia, and had a lower fluid balance compared to the control group. Conclusions Automated anesthetic management using the combination of three controllers outperforms manual control and may have an impact on delayed neurocognitive recovery. However, given the study design, it is not possible to determine the relative contribution of each controller on the cognition score.

Editor’s Perspective What We Already Know about This Topic Modern ventilation approaches use a bundle of lower tidal volumes, lower driving pressures, and positive end-expiratory pressure The contributions of each component to reducing postoperative pulmonary complications in an adult cardiac surgical population is not known What This Article Tells Us That Is New In this retrospective analysis, the intraoperative ventilation bundle was associated with a lower rate of postoperative pulmonary complications Lower modified driving pressure was independently associated with fewer pulmonary complications Background Compared with historic ventilation strategies, modern lung-protective ventilation includes lower tidal volumes (V T ), lower driving pressures, and application of positive end-expiratory pressure (PEEP). The contributions of each component to an overall intraoperative protective ventilation strategy aimed at reducing postoperative pulmonary complications have neither been adequately resolved, nor comprehensively evaluated within an adult cardiac surgical population. The authors hypothesized that a bundled intraoperative protective ventilation strategy was independently associated with decreased odds of pulmonary complications after cardiac surgery. Methods In this observational cohort study, the authors reviewed nonemergent cardiac surgical procedures using cardiopulmonary bypass at a tertiary care academic medical center from 2006 to 2017. The authors tested associations between bundled or component intraoperative protective ventilation strategies (V T below 8 ml/kg ideal body weight, modified driving pressure [peak inspiratory pressure − PEEP] below 16 cm H 2 O, and PEEP greater than or equal to 5 cm H 2 O) and postoperative outcomes, adjusting for previously identified risk factors. The primary outcome was a composite pulmonary complication; secondary outcomes included individual pulmonary complications, postoperative mortality, as well as durations of mechanical ventilation, intensive care unit stay, and hospital stay. Results Among 4,694 cases reviewed, 513 (10.9%) experienced pulmonary complications. After adjustment, an intraoperative lung-protective ventilation bundle was associated with decreased pulmonary complications (adjusted odds ratio, 0.56; 95% CI, 0.42–0.75). Via a sensitivity analysis, modified driving pressure below 16 cm H 2 O was independently associated with decreased pulmonary complications (adjusted odds ratio, 0.51; 95% CI, 0.39–0.66), but V T below 8 ml/kg and PEEP greater than or equal to 5 cm H 2 O were not. Conclusions The authors identified an intraoperative lung-protective ventilation bundle as independently associated with reduced pulmonary complications after cardiac surgery. The findings offer insight into components of protective ventilation associated with adverse outcomes and may serve as targets for future prospective interventional studies investigating the impact of specific protective ventilation strategies on postoperative outcomes after cardiac surgery.

Editor’s Perspective What We Already Know about This Topic Higher driving pressure during controlled mechanical ventilation is known to be associated with increased mortality in patients with acute respiratory distress syndrome. Whereas patients with acute respiratory distress syndrome are initially managed with controlled mechanical ventilation, as they improve, they are transitioned to assisted ventilation. Whether higher driving pressure assessed during pressure support (assisted) ventilation can be reliably assessed and whether higher driving pressure is associated with worse outcomes in patients with acute respiratory distress syndrome has not been well studied. What This Article Tells Us That Is New This study shows that in the majority of adult patients with acute respiratory distress syndrome, both driving pressure and respiratory system compliance can be reliably measured during pressure support (assisted) ventilation. Higher driving pressure measured during pressure support (assisted) ventilation significantly associates with increased intensive care unit mortality, whereas peak inspiratory pressure does not. Lower respiratory system compliance also significantly associates with increased intensive care unit mortality. Background Driving pressure, the difference between plateau pressure and positive end-expiratory pressure (PEEP), is closely associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). Although this relationship has been demonstrated during controlled mechanical ventilation, plateau pressure is often not measured during spontaneous breathing because of concerns about validity. The objective of the present study is to verify whether driving pressure and respiratory system compliance are independently associated with increased mortality during assisted ventilation ( i.e ., pressure support ventilation). Methods This is a retrospective cohort study conducted on 154 patients with ARDS in whom plateau pressure during the first three days of assisted ventilation was available. Associations between driving pressure, respiratory system compliance, and survival were assessed by univariable and multivariable analysis. In patients who underwent a computed tomography scan (n = 23) during the stage of assisted ventilation, the quantity of aerated lung was compared with respiratory system compliance measured on the same date. Results In contrast to controlled mechanical ventilation, plateau pressure during assisted ventilation was higher than the sum of PEEP and pressure support (peak pressure). Driving pressure was higher (11 [9–14] vs . 10 [8–11] cm H 2 O; P = 0.004); compliance was lower (40 [30–50] vs. 51 [42–61] ml · cm H 2 O -1 ; P < 0.001); and peak pressure was similar, in nonsurvivors versus survivors. Lower respiratory system compliance (odds ratio, 0.92 [0.88–0.96]) and higher driving pressure (odds ratio, 1.34 [1.12–1.61]) were each independently associated with increased risk of death. Respiratory system compliance was correlated with the aerated lung volume (n = 23, r = 0.69, P < 0.0001). Conclusions In patients with ARDS, plateau pressure, driving pressure, and respiratory system compliance can be measured during assisted ventilation, and both higher driving pressure and lower compliance are associated with increased mortality.

This fourth and last installment of my history of basic airway management discusses the current ( i.e. , “modern”) era of anesthesia and resuscitation, from 1960 to the present. These years were notable for the implementation of intermittent positive pressure ventilation inside and outside the operating room. Basic airway management in cardiopulmonary resuscitation ( i.e. , expired air ventilation) was de-emphasized, as the “A-B-C” (airway-breathing-circulation) protocol was replaced with the “C-A-B” (circulation-airway-breathing) intervention sequence. Basic airway management in the operating room ( i.e. , face-mask ventilation) lost its predominant position to advanced airway management, as balanced anesthesia replaced inhalation anesthesia. The one-hand, generic face-mask ventilation technique was inherited from the progressive era. In the new context of providing intermittent positive pressure ventilation, the generic technique generated an underpowered grip with a less effective seal and an unspecified airway maneuver. The significant advancement that had been made in understanding the pathophysiology of upper airway obstruction was thus poorly translated into practice. In contrast to consistent progress in advanced airway management, progress in basic airway techniques and devices stagnated.

A novel approach to ventilation aims to be both lung- and diaphragm-protective. This strategy integrates concerns over excessive lung stress during spontaneous breathing while avoiding both insufficient and excessive inspiratory effort.

This third installment of the history of basic airway management discusses the transitional—“progressive”—years of anesthesia from 1904 to 1960. During these 56 yr, airway management was provided primarily by basic techniques with or without the use of a face mask. Airway maneuvers were inherited from the artisanal era: head extension and mandibular advancement. The most common maneuver was head extension, also used in bronchoscopy and laryngoscopy. Basic airway management success was essential for traditional inhalation anesthesia (ether, chloroform) and for the use of the new anesthetic agents (cyclopropane, halothane) and intravenous drugs (thiopental, curare, succinylcholine). By the end of the era, the superiority of intermittent positive pressure ventilation to spontaneous ventilation in anesthesia and negative pressure ventilation in resuscitation had been demonstrated and accepted, and the implementation of endotracheal intubation as a routine technique was underway.

Background Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (V A /Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of V A /Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by V A /Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model. Methods Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. V A /Q distribution was assessed by the multiple inert gas elimination technique. Results Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min. Conclusions Inhaled methacholine induced bronchoconstriction and inhomogeneous V A /Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

Background One important explanation for the detrimental effects of conventional mechanical ventilation is the biotrauma hypothesis that ventilation may trigger proinflammatory responses that subsequently cause lung injury. This hypothesis has frequently been studied in so-called one-hit models (overventilation of healthy lungs) that so far have failed to establish an unequivocal link between inflammation and hypoxemic lung failure. This study was designed to develop a one-hit biotrauma model. Methods Mice (six per group) were ventilated for up to 7 h (positive end-expiratory pressure 2 cm H 2 O) and received 300 μl/h fluid support. Series_1: initial plateau pressures of 10, 24, 27, or 30 cm H 2 O. Series_2: ventilation with pressure release at 34 cm H 2 O and initial plateau pressure of 10, 24, 27, or 30 cm H 2 O. To study the significance of inflammation, the latter groups were also pretreated with the steroid dexamethasone. Results Within 7 h, 20 of 24 mice ventilated with plateau pressure of 27 cm H 2 O or more died of a catastrophic lung failure characterized by strongly increased proinflammatory markers and a precipitous decrease in pulmonary compliance, blood pressure, and oxygenation. Pretreatment with dexamethasone reduced inflammation, but prolonged median survival time by 30 min. Conclusions Our findings demonstrate a sharp distinction between ventilation with 24 cm H 2 O that was well tolerated and ventilation with 27 cm H 2 O that was lethal for most animals due to catastrophic lung failure. In the former case, inflammation was benign and in the latter, a by-product that only accelerated lung failure. The authors suggest that biotrauma—when defined as a ventilation-induced and inflammation-dependent hypoxemia—is difficult to study in murine one-hit models of ventilation, at least not within 7 h. (Anesthesiology 2017; 126:909-22)

Background Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol’s respiratory effects. Methods Twelve healthy male volunteers received 600 μg oral cebranopadol as a single dose. The following main endpoints were obtained at regular time intervals for 10 to 11 h after drug intake: ventilation at an elevated clamped end-tidal pressure of carbon dioxide, pain threshold and tolerance to a transcutaneous electrical stimulus train, and plasma cebranopadol concentrations. The data were analyzed using sigmoid Emax (respiration) and power (antinociception) models. Results Cebranopadol displayed typical opioid-like effects including miosis, analgesia, and respiratory depression. The blood-effect-site equilibration half-life for respiratory depression and analgesia was 1.2 ± 0.4 h (median ± standard error of the estimate) and 8.1 ± 2.5 h, respectively. The effect-site concentration causing 50% respiratory depression was 62 ± 4 pg/ml; the effect-site concentration causing 25% increase in currents to obtain pain threshold and tolerance was 97 ± 29 pg/ml. The model estimate for minimum ventilation was greater than zero at 4.9 ± 0.7 l/min (95% CI, 3.5 to 6.6 l/min). Conclusions At the dose tested, cebranopadol produced respiratory depression with an estimate for minimum ventilation greater than 0 l/min. This is a major advantage over full μ-opioid receptor agonists that will produce apnea at high concentrations. Further clinical studies are needed to assess whether such behavior persists at higher doses.